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排序方式: 共有181条查询结果,搜索用时 15 毫秒
81.
Meur G Qian Q da Silva Xavier G Pullen TJ Tsuboi T McKinnon C Fletcher L Tavaré JM Hughes S Johnson P Rutter GA 《The Journal of biological chemistry》2011,286(15):13647-13656
82.
Lo HY Nemoto PA Kim JM Hao MH Qian KC Farrow NA Albaugh DR Fowler DM Schneiderman RD Michael August E Martin L Hill-Drzewi M Pullen SS Takahashi H De Lombaert S 《Bioorganic & medicinal chemistry letters》2011,21(15):4533-4539
A new class of chymase inhibitor featuring a benzimidazolone core with an acid side chain and a P1 hydrophobic moiety is described. Incubation of the lead compound with GSH resulted in the formation of a GSH conjugate on the benzothiophene P1 moiety. Replacement of the benzothiophene with different heterocyclic systems such as indoles and benzoisothiazole is feasible. Among the P1 replacements, benzoisothiazole prevents the formation of GSH conjugate and an in silico analysis of oxidative potentials agreed with the experimental outcome. 相似文献
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84.
AI Tarasov F Semplici MA Ravier EA Bellomo TJ Pullen P Gilon I Sekler R Rizzuto GA Rutter 《PloS one》2012,7(7):e39722
Glucose induces insulin release from pancreatic β-cells by stimulating ATP synthesis, membrane depolarisation and Ca(2+) influx. As well as activating ATP-consuming processes, cytosolic Ca(2+) increases may also potentiate mitochondrial ATP synthesis. Until recently, the ability to study the role of mitochondrial Ca(2+) transport in glucose-stimulated insulin secretion has been hindered by the absence of suitable approaches either to suppress Ca(2+) uptake into these organelles, or to examine the impact on β-cell excitability. Here, we have combined patch-clamp electrophysiology with simultaneous real-time imaging of compartmentalised changes in Ca(2+) and ATP/ADP ratio in single primary mouse β-cells, using recombinant targeted (Pericam or Perceval, respectively) as well as entrapped intracellular (Fura-Red), probes. Through shRNA-mediated silencing we show that the recently-identified mitochondrial Ca(2+) uniporter, MCU, is required for depolarisation-induced mitochondrial Ca(2+) increases, and for a sustained increase in cytosolic ATP/ADP ratio. By contrast, silencing of the mitochondrial Na(+)-Ca(2+) exchanger NCLX affected the kinetics of glucose-induced changes in, but not steady state values of, cytosolic ATP/ADP. Exposure to gluco-lipotoxic conditions delayed both mitochondrial Ca(2+) uptake and cytosolic ATP/ADP ratio increases without affecting the expression of either gene. Mitochondrial Ca(2+) accumulation, mediated by MCU and modulated by NCLX, is thus required for normal glucose sensing by pancreatic β-cells, and becomes defective in conditions mimicking the diabetic milieu. 相似文献
85.
Karine Malagu Heather Duggan Keith Menear Marc Hummersone Sylvie Gomez Christine Bailey Peter Edwards Jan Drzewiecki Frédéric Leroux Mar Jimenez Quesada Gesine Hermann Stephanie Maine Carrie-Anne Molyneaux Armelle Le Gall James Pullen Ian Hickson Lisa Smith Sharon Maguire Niall Martin Graeme Smith Martin Pass 《Bioorganic & medicinal chemistry letters》2009,19(20):5950-5953
We describe a novel series of potent inhibitors of the kinase activity of mTOR. The compounds display good selectivity relative to other PI3K-related kinase family members and, in cellular assays, inhibit both mTORC1 and mTORC2 complexes and exhibit good antiproliferative activity. 相似文献
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Receptor activity modifying proteins interaction with human and porcine calcitonin receptor-like receptor (CRLR) in HEK-293 cells 总被引:3,自引:0,他引:3
Aiyar Nambi Disa Jyoti Pullen Mark Nambi Ponnal 《Molecular and cellular biochemistry》2001,224(1-2):123-133
Calcitonin gene-related peptide (CGRP) and adrenomedullin (ADM), two closely related peptides, initiate their biological responses through their interaction with calcitonin receptor-like receptor (CRLR). The CRLR receptor phenotype can be determined by coexpression of CRLR with one of the three-receptor activity modifying proteins (RAMPs). In this report, we characterized the pharmacological properties of the human or porcine CRLR with individual RAMPs transiently expressed in human embroynic kidney cell line (HEK-293). Characterization of RAMP1/human or porcine CRLR combination by radioligand binding ([125I] hCGRP) and functional assay (activation of adenylyl cyclase) revealed the properties of CGRP receptor. Similarly characterization of RAMP2/human or porcine CRLR and RAMP3/human or porcine CRLR combination by radioligand binding ([125I]rADM) and functional assay (activation of adenylyl cyclase) revealed the properties of ADM (22–52) sensitive-ADM receptor. In addition, porcine CRLR/RAMP2 or 3 combination displayed specific high affinity [125I] hCGRP binding also. Also, co-transfection of porcine CRLR with RAMPs provided higher expression level of the receptor than the human counterpart. Thus the present study along with earlier studies strongly support the role of RAMPs in the functional expression of specific CRLRs. 相似文献
90.
Bearder SK Ambrose L Harcourt C Honess P Perkin A Pimley E Pullen S Svoboda N 《Folia primatologica; international journal of primatology》2003,74(5-6):337-354
This paper provides a checklist and summary of what is currently known of the variation in infant contact, sleeping site preference and aspects of social cohesion in the nocturnal primates of Africa. Genera and species are compared, based on previously unpublished field observations and a review of the literature. There is a clear pattern of similarity between the species within each genus and distinct differences between genera. Species in the same genus tend to be ecologically equivalent and replace each other allopatrically, whereas species in different genera are more likely to be sympatric, with up to 6 species living together. Maximum sympatry within genera is found in Otolemur and Galagoides, where species are ecologically divergent. This may reflect an ancient origin of species within these genera or suggest that further taxonomic revision is required at the generic level. Some data are recorded for the first time for species that have only recently been separated (cryptic species), but some taxa remain very poorly known. It is concluded that field studies are still at an elementary stage and further research with radio tracking is urgently needed in the face of rapidly declining habitats. 相似文献